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Archive - 2011

October 28th

Genetic Risk Factor Identified for Major Depression

Scientists at the Texas Biomedical Research Institute and Yale University have identified a new target area in the human genome that appears to harbor genes with a major role in the onset of depression. Using the power of Texas Biomed’s AT&T Genomics Computing Center (GCC), the researchers found the region by devising a new method for analyzing thousands of potential risk factors for this complex disease, a process that led them to a new biomarker that may be helpful in identifying people at risk for major depression. “We were searching for things in psychiatric disease that are the equivalent of what cholesterol is to heart disease,” said Dr. John Blangero, director of the GCC and a principal investigator in the study. “We wanted to find things that can be measured in everybody and that can tell you something about risk for major depression.” The study was directed by Dr. Blangero and Dr. David Glahn, of Yale University. It was published online on October 7, 2011 in the journal Biological Psychiatry and supported by the National Institutes of Health. Major depressive disorder is one of the most common and most costly mental illnesses. Studies have estimated that up to 17 percent of Americans will suffer depression at some point in their lives. The disorder has proven to be a tough challenge for geneticists. Despite strong evidence that people can inherit a susceptibility to major depression, years of study have failed to locate any of the key genes that underlie the illness. In this study, the scientists used blood samples from 1,122 people enrolled in the Genetics of Brain Structure and Function Study, a large family study that involves people from 40 extended Mexican American families in the San Antonio area. Dr.

New Oncolytic Virus Shows Promise for Treatment of Brain Cancer

A new, fourth-generation oncolytic virus designed to both kill cancer cells and inhibit blood-vessel growth has shown greater effectiveness than earlier versions when tested in animal models of human brain cancer. Researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) are developing the oncolytic virus as a treatment for glioblastoma, the most common and deadly form of brain cancer (average survival: 15 months after diagnosis). The new oncolytic virus, called 34.5ENVE, improved survival of mice with transplanted human glioblastoma tumors by 50 percent in a majority of cases compared with the previous-generation oncolytic virus. The study was published online on October 25, 2011 in the journal Molecular Therapy. “These findings show the amazing therapeutic efficacy of this new oncolytic virus against four different glioblastoma models in animals,” says cancer researcher Dr. Balveen Kaur, associate professor of neurological surgery, and a member of the OSUCCC – James viral oncology research program. The new oncolytic virus is engineered to replicate in cells that express the protein nestin. First identified as a marker for neuronal stem cells, nestin is also expressed in glioblastoma and other malignancies, including gastrointestinal, pancreatic, prostate, and breast cancer. “We believe that nestin-driven oncolytic viruses will prove valuable for the treatment of many types of cancer,” Dr. Kaur says. The new oncolytic virus also carries a gene to inhibit tumor blood-vessel growth. That gene, called Vstat120, was added to increase the virus’s anti-tumor effectiveness and prolong the virus’s presence within tumors.

Scientists Identify Stem Cell Key to Lung Regeneration

Scientists at A*STAR (Agency for Science, Technology, and Research)’s Genome Institute of Singapore (GIS) and Institute of Molecular Biology (IMB), together with colleagues, have made a breakthrough discovery in the understanding of lung regeneration. Their research showed for the first time that distal airway stem cells (DASCs), a specific type of stem cells in the lungs, are involved in forming new alveoli to replace and repair damaged lung tissue, providing a firm foundation for understanding lung regeneration. The new research was reported in the October 28, 2011 issue of Cell. Lung damage is caused by a wide range of lung diseases including influenza infections and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Influenza infection induces acute respiratory distress syndrome (ARDS) which affects more than 150,000 patients a year in the US, with a death rate of up to 50 percent. COPD is the fifth biggest killer worldwide. The research team took a novel approach in tackling the question of lung regeneration. They cloned adult stem cells taken from three different parts of the lungs - nasal epithelial stem cells (NESCs), tracheal airway stem cells (TASCs), and distal airway stem cells (DASCs). Despite the three types of cells being nearly 99 percent genetically identical, the team made the surprising observation that only DASCs formed alveoli when cloned in vitro. "We are the first researchers to demonstrate that adult stem cells are intrinsically committed and will only differentiate into the specific cell type they originated from. In this case, only DASCs formed alveoli because alveolar cells are found in the distal airways, not in the nasal epithelial or tracheal airway," said Dr Wa Xian, Principal Investigator at IMB.

October 27th

Available Drug May Help in Polycystic Kidney Disease, Mouse Studies Show

Scientists at the University of California-Santa Barbara (UCSB) and the University of Toronto have discovered that patients with an inherited kidney disease may be helped by a drug that is currently available for other uses. The findings were published online on October 24, 2011 in the Proceedings of the National Academy of Sciences. Over 600,000 people in the United States, and 12 million worldwide, are affected by the inherited kidney disease known as autosomal-dominant polycystic kidney disease (ADPKD). The disease is characterized by the proliferation of thousands of cysts that eventually debilitate the kidneys, causing kidney failure in half of all patients by the time they reach age 50. ADPKD is one of the leading causes of renal failure in the United States. "Currently, no treatment exists to prevent or slow cyst formation, and most ADPKD patients require kidney transplants or lifelong dialysis for survival," said Dr. Thomas Weimbs, director of the laboratory at UCSB where the discovery was made. Dr. Weimbs is an associate professor in the Department of Molecular, Cellular and Developmental Biology, and in the Neuroscience Research Institute at UCSB. Recent work in the Weimbs laboratory has revealed a key difference between kidney cysts and normal kidney tissue. They found that the STAT6 signaling pathway –– previously thought to be mainly important in immune cells –– is activated in kidney cysts, while it is dormant in normal kidneys. Cystic kidney cells are locked in a state of continuous activation of this pathway, which leads to the excessive proliferation and cyst growth in ADPKD. The drug leflunomide, which is clinically approved for use in rheumatoid arthritis, has previously been shown to inhibit the STAT6 pathway in cells.

Genome of Giant Parasitic Roundworm Sequenced

Scientists have identified the genetic blueprint of the giant intestinal roundworm, Ascaris suum, revealing potential targets to control the devastating parasitic disease, ascariasis, which affects more than one billion people in China, South East Asia, South America, and parts of Africa, killing thousands of people annually and causing chronic effects in young children. Dr Aaron Jex and Professor Robin Gasser, both from the University of Melbourne's Faculty of Veterinary Science, led the international research project, the results of which were published online on October 26, 2011 in the journal Nature. The work has provided new insights into how to treat ascariasis, identified by the World Health Organization as a key, neglected disease in urgent need of extensive research and significantly improved control. "Sequencing the genome of Ascaris suum is a major step towards controlling the infection it causes because the more we know about the genetics of the parasite and how it works, the better we can fight it with novel treatments," Dr. Jex said. "From the genome sequence we have identified five high-priority drug targets that are likely to be relevant for many other parasitic worms. New treatments are urgently needed and genome-guided drug target discovery is ideal for identifying targets that selectively kill the parasite and not the host. We also identified key information on how the parasite hides from the immune system, which is essential for any future vaccine development." The team sequenced the nuclear genome of Ascaris sum, which is an easier worm to study in the laboratory and mainly only infects pigs, but is very closely related to Ascaris lumbricoides, which causes ascariasis in humans. The worms range from 15-30 cm in length and are spread via eggs in contaminated food.

Python Study May Have Implications for Human Heart Health

A surprising new University of Colorado-Boulder study shows that huge amounts of fatty acids circulating in the bloodstreams of feeding pythons promote healthy heart growth, results that may have implications for treating human heart disease. CU-Boulder Professor Leslie Leinwand and her research team found the amount of triglycerides -- the main constituent of natural fats and oils -- in the blood of Burmese pythons one day after eating increased by more than fifty-fold. Despite the massive amount of fatty acids in the python bloodstream, there was no evidence of fat deposition in the heart, and the researchers also saw an increase in the activity of a key enzyme known to protect the heart from damage. After identifying the chemical make-up of blood plasma in fed pythons, the CU-Boulder researchers injected fasting pythons with either "fed python" blood plasma or a reconstituted fatty acid mixture they developed to mimic such plasma. In both cases, the pythons showed increased heart growth and indicators of cardiac health. The team took the experiments a step farther by injecting mice with either fed python plasma or the fatty acid mixture, with the same results. "We found that a combination of fatty acids can induce beneficial heart growth in living organisms," said CU-Boulder postdoctoral researcher Dr. Cecilia Riquelme, first author on the research article being published in the October 28, 2011 issue of the journal Science. In addition to Drs. Leinwand and Riquelme, the authors include CU postdoctoral researcher Dr. Brooke Harrison, CU graduate student Jason Magida, CU undergraduate Christopher Wall, Hiberna Corp. researcher Dr. Thomas Marr, and University of Alabama Tuscaloosa Professor Stephen Secor.

Potential New Drug Target for Prevention of Physical Disability in MS

Medical researchers at the University of Alberta in Canada have discovered a potential new drug target for multiple sclerosis (MS) that could prevent physical disability associated with the disease, once a new drug is developed. In the first phase of MS, those with the condition have significant inflammation of their brain cells, resulting in continuous cycles of inflammation attacks followed by recovery periods. In the second phase of the disease, the inflammation isn't as severe, but this is the stage where physical disability sets in due to the effects from substantial numbers of brain cells having been killed in the first phase of the disease. When immune cells become active due to inflammation, they can pass through the blood-brain barrier and enter the central nervous system. Some of these activated immune cells secrete a molecule, known as granzyme B, that can get inside neurons and wreak havoc – ultimately causing brain cell death. Granzyme B is found in MS brain lesions – especially in the early stages of inflammation. This molecule can get into brain cells through a "gatekeeper," known as receptor M6PR. Researchers with the Faculty of Medicine & Dentistry at the University of Alberta discovered in lab experiments that if they prevent this granzyme B from entering neurons, "we can also prevent the killing of neurons," says principal investigator Dr. Fabrizio Giuliani, whose team’s work was published online on September 30, 2011 in The Journal of Immunology. "It is this loss of brain cells, in the long-term, which induces disability in those with MS," Dr. Giuliani says. "This is a new drug target for MS that is specific for the neurodegenerative processes following inflammation." Dr.

October 26th

Study Examines Compensatory Up-Regulation of X Chromosome

In a study published online on October 23, 2011 in the journal Nature Genetics, a group of scientists including University of North Carolina (UNC) biologist Dr. Jason Lieb, present experiments supporting a longstanding hypothesis that explains how males can survive with only one copy of the X chromosome. The finding provides clarity to a hotly debated topic in science and provides biologists with more information to interpret experiments involving genetic measurements in males and females. "The issue is important because many diseases are tied to a defect in a regulatory mechanism within the cell," said Dr. Lieb, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Women have two X chromosomes, while men have one X and one Y. The lack of a “back up” copy of the X chromosome in males contributes to many disorders that have long been observed to occur more often in males, such as hemophilia, Duchene muscular dystrophy, and certain types of color blindness. Having only one copy of X and two copies of every other chromosome also creates a more fundamental problem – with any other chromosome, the gene number imbalance resulting from having only one copy would be lethal. How can males survive with only one X? Biologists have been debating how organisms and cells manage the imbalance between X and other chromosomes for years, with the dominant theory being that both sexes up-regulate the expression of X-linked genes, essentially doubling their expression to "2X" in males and "4X" in females. Then, to correct the imbalance that now appears in females (because they have the equivalent of "4" Xs now and 2 of every other chromosome), females then 'turn off' one of the hyperactive X chromosomes, resulting in a balanced "2X" expression of those genes across both sexes.

Exome Sequencing Reveals Mutation Associated with Hearing Impairment

Researchers have used the power of next-generation sequencing to identify a gene involved in hearing impairment in a mouse study. The findings reveal a new and unexpected function for a previously well-studied gene. The study, published on September 21, 2011 in Genome Biology, found that this mutation is involved in otitis media, an inflammation of the middle ear, which is a prominent cause of hearing impairment especially in children. This research highlights the power of genome sequencing to identify causative mutations. "Otitis media is the leading cause of surgery in children in the developed world. It affects 35% of children under the age of 2 in Europe," explains Dr. Jennifer Hilton, from the Wellcome Trust Sanger Institute and first author on the paper. "With these expanding developments in the genetics and the understanding of otitis media, there is a possibility of reducing the need for invasive surgery in young children in the future." This research emphasizes two important concepts. Firstly, exome sequencing can detect mutations that increase the chances of developing a disease but don't necessarily cause the problem in every person carrying the mutation (a phenomenon known as reduced penetrance). Secondly, the middle ear disease was detected only because the researchers looked for it, and could easily be missed in a mouse, suggesting that we only find what we look for in mouse models of disease. The team studied the exome sequence of one affected mouse and found a mutation in the Islet1 gene. They then looked for this mutation in a collection of affected mice and found that all contained the mutation in the Islet1 gene. The mutants show a thickened and inflamed lining of the middle ear and excessive fluid and cell debris in what should be an air-filled middle ear cavity, which is a clear indication of chronic otitis media.

Imperial Woodpecker Takes Flight in Recovered Film

It was once the undisputed king of its clan, but most believe the imperial woodpecker faded unseen into the pages of history sometime in the late 20th century in the high mountains of Mexico. But now, thanks to some keen detective work, the largest woodpecker that ever lived can be seen by the world once more – and this 85-second flight through time offers us a lesson about its behavior, and ours. "It is stunning to look back through time with this film and see the magnificent imperial woodpecker moving through its old-growth forest environment,” said research associate Dr. Martjan Lammertink, lead author of a paper describing the detective work, written along with four Cornell Lab of Ornithology staff members and two Mexican biologists. "And it is heartbreaking to know that both the bird and the forest are gone." The imperial woodpecker was thought to have gone extinct without anyone ever capturing photos or film of the 2-foot-tall, flamboyantly crested bird. That was until a biologist from the Cornell Lab of Ornithology tracked down a 16-mm film shot in 1956 by a dentist from Pennsylvania. The footage, which captures the last confirmed sighting of an imperial woodpecker in the wild, is available for viewing at http://www.birds.cornell.edu/imperialfilm. In the color film, a female imperial woodpecker hitches up and forages on the trunks of large Durango pines and then launches into flight. The film was shot by William Rhein with a hand-held camera from the back of a mule while camping in a remote location in the Sierra Madre Occidental in Durango state. In March 2010, Dr. Lammertink and Dr. Tim Gallagher of the Cornell Lab launched an expedition with members of the conservation group Pronatura Noroeste to identify and survey the film site.